Microbially derived essential amino acids compensate for dietary deficiencies in an ecologically relevant mammalian host.

Protein is the main structural and functional component of cells, making it crucial for the survival of all living organisms. Yet mammalian herbivores and omnivores often consume diets deficient in the amount of protein required for growth, homeostasis, and reproduction. To compensate, mammals likely rely on their gut microbiota to synthesize essential amino acids (AAESS), particularly during periods of dietary protein limitation. We quantified the contribution of microbially synthesized AAESS to skeletal muscle in captive, wild-derived deer mice (Peromyscus maniculatus) fed diets varying in macromolecular quantity and quality. Using amino acid carbon isotope (δ13C) analysis combined with genetic sequencing, we assessed the origin of AAESS incorporated into host muscle and identified gut microbial taxa with the genetic potential for AAESS biosynthesis. We estimate that up to 25% of host muscle AAESS were microbially derived, with greater microbial contributions in mice fed diets containing low protein or more complex macronutrients. Gut microbial populations with the genetic potential for AAESS biosynthesis were more abundant in mice with larger contributions of microbially-derived AAESS in their tissues. These results demonstrate the crucial and likely pervasive role the gut microbiome plays in host protein metabolism, especially in mammals facing seasonal or persistent dietary protein limitation.